This invention relates to receptor-activated. reporter systems.
Many disease processes adversely affect the normal operation of membrane receptor systems that deliver signals for regulating cellular functions. Effective therapy for such diseases includes drugs that directly interact with the receptor systems in a way that counters the affect of a particular disease process. Even diseases that do not directly affect a receptor signaling mechanism can be fully or partially alleviated by exogenously manipulating signaling by appropriate receptors through drug therapy. Based on these principles, notable successes have been achieved in designing effective drugs to alleviate illnesses, including anti-depressants and anti-ulcer drugs.
Many diseases for which no effective therapy exists can also be approached by developing drugs that would interact directly with appropriate receptor systems. These include but are not limited to the insulin receptor signaling systems in muscle, which are defective in Type II diabetes mellitus, the PDGF and IGF-I receptor signaling systems which appear to stimulate abnormal proliferation of smooth muscle cells in coronary artery disease, and lymphokine receptors which mediate inappropriate autoimmune reactions. Development of appropriate drugs that directly effect these and other receptor proteins need to be generated. Efficient development of such drugs require screening of compounds with biological assays that selectively and, perhaps more importantly, efficiently monitor specific receptor activities in response to drug action. In such assays, it is necessary to have a highly sensitive, convenient readout of receptor activity. This disclosure describes discoveries capable of providing such a readout for the activity of the insulin receptor as well as many other receptor systems.